day 1 - liver and enzymes Flashcards
potential causes of Raised serum enzymes
Increased synthesis, including cell proliferation Tissue damage enzyme type indicates tissue source level indicates rate/amount of damage Cell death Defective clearance (“macro-enzymes”)
potential causes of Low enzyme activity
Artefactual - EDTA, citrate particularly important for inborn errors where gene defect may affect: - active site - Synthesis of enzyme Co-enzyme defect/deficiency
a potential problem with using the lab quoted reference range
Laboratory may not quote age/sex adjusted reference range on report.
Range probably for healthy adult
User must vary interpretation as required e.g. if a child, particular issue with ALP as this spikes during adolensence
Even if laboratory does quote age/sex range may still be other variation factors eg,
- ALP in later pregnancy (increases)
- CK in different ethnic groups (higher in Afro-Caribbean)
causes of raised creatine kinase
Myocardial infarction
- timing and practicalities of use (peaks at 24hrs and gone by 48 hrs)
- Superseded by Troponins
Rhabdomyolysis
- More sensitive than urine myoglobin
Hypothyroidism
Post exercise
Statin-induced myositis
Dystrophies (v. high CK)
use and problems of amylase
Isoenzymes: Salivary and pancreatic
Main use
- large rise in acute pancreatitis
- 10X ULN (upper limit of normal) in patient with acute abdomen virtually diagnostic
Problems
acute overuse (don’t need to measure daily)
Other causes of raised levels (e.g. mumps,CKD)
- macroamylase!
what is macroamylase
= Persistently elevated amylase with no clinical reason
- Check urine. If not raised probably due to macroamylase
=amylase + immunoglobulin, too big to be cleared by the kidney
N.B. Can get macro forms of many enzymes and proteins (macroCK, macroprolactin etc)
- If something doesn’t fit with the clinical picture, discuss with duty biochemist
major functions of the liver
Metabolism of: -Carbohydrate - Gluconeogenesis, glycogenolysis Lipid - Synthesis, metabolism Protein - Synthesis and catabolism Hormones - mainly inactivation drugs/toxins - activation/metabolism Immunological function Storage - e.g. glycogen
‘LFT’ request @UCLH includes
Bilirubin
Albumin
Alanine transaminase (ALT)
Alkaline phosphatase (ALP)
use of bilirubin as a test of liver excretory capacity
Bilirubin is one in vivo test of liver excretory capacity.
10-fold reserve capacity of liver makes it relatively insensitive.
Necessary to understand stages in bilirubin metabolism because things can go wrong at each stage.
different types of bilirubin
Serum bilirubin (3-17 umol/L)
Serum conjugated bilirubin 0-3 umol/L
Urine bilirubin - not normally detected
Urine urobilinogen
what is bilirubin
Bilirubin (formerly referred to as haematoidin) is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases. It is responsible for the yellow color of bruises, the background straw-yellow color of urine via its reduced breakdown product, urobilin (the more obvious but variable bright yellow color of urine is due to thiochrome, a breakdown product of thiamine), the brown color of feces (via its conversion to stercobilin), and the yellow discoloration in jaundice.
the production of unconjugated bilirubin
Erythrocytes (red blood cells) generated in the bone marrow are disposed of in the spleen when they get old or damaged. This releases hemoglobin, which is broken down to heme as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the monocyte macrophages system of the spleen. This unconjugated bilirubin is not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin and sent to the liver.
processing of unconjugated bilirubin once it reaches the liver
In the liver, bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water: the conjugated version is also often called “direct” bilirubin.
Prematurity, Crigler-Najar syndrome (congenital enzyme deficiency), some patients with Gilbert’s syndrome (partial enzyme deficiency), inhibition by novobiocin or breast-milk steroids, can all interfere with bilirubin conjugation.
excretion of conjugated bilirubin from the liver
Excretion across the microvilli into the biliary canaliculi, where bilirubin is complexed with bile salts, phospholipids and cholesterol; and conveyed by the common bile duct into the small intestine.
Mechanical obstruction by cirrhosis, hepatitis, tumour, gallstone in the common bile duct, or carcinoma of the head of the pancreas may cause jaundice, as may interference by chlorpromazine, or the congenital Dubin-Johnson and Rotor syndromes.
processing of conjugated bilirubin in the intestines
In the large intestine, bilirubin is hydrolysed by bacterial enzymes to colourless urobilinogen ( which can be oxidized to form urobilin and stercobilin: these give stool its characteristic brown color.).
In patients taking antibiotics to sterilise the gut prior to surgery, there may be an absence of urobilinogen from the urine.
Urobilinogen is reabsorbed from the portal circulation by the liver, and re-excreted (enterohepatic circulation). Some enters the systemic circulation for excretion by kidneys.
In the pre-icteric stage of viral hepatitis, there can be a marked increase in urinary urobilinogen as the liver fails to take up urobilinogen from the portal circulation, leaving more to be excreted by the kidneys.
